Antibody response to islet antigens in anti-CD4/prednisolone immune intervention of type 1 diabetes

Abstract

Cytoplasmic islet cell antibodies, glutamic acid decarboxylase autoantibodies, spontaneous insulin autoantibodies, and insulin-induced antibodies were analyzed in a 1-year follow-up study of 12 newly diagnosed patients with insulin-dependent diabetes mellitus aged 14 +/- 2 years (range 7-20 years) who had been initially treated with either multiple injections of insulin alone (control group) or, in addition, anti-CD4 monoclonal antibody/prednisolone (treatment group). Despite individual variations in islet cell antibody titers, there were no significant differences in the prevalence or changes in the mean titers between the two groups. Glutamic acid decarboxylase autoantibodies remained almost unchanged, but correlated with levels of islet cell antibodies. While at initiation of treatment only 50% of the patients from both groups had spontaneous insulin autoantibodies, all patients developed insulin-induced antibodies upon conventional insulin therapy during the course of follow-up. This was not related to islet cell antibody or glutamic acid decarboxylase antibody levels. The insulin requirement was markedly reduced through the period of follow-up, but did not significantly differ between the two groups. A correlation between islet cell antibody levels and insulin requirement was observed in the control group but not in the treatment group. Plasma levels of the antibodies were not associated with changes in stimulated C-peptide or hemoglobin A1 concentrations. Activated T-lymphocytes persisted in both groups of patients, but their mean levels were not significantly different. The reason for the absence of statistically significant differences between treatment and control groups could be due to the small number of patients in the study. In conclusion, short-term immune intervention with anti-CD4 monoclonal antibody in addition to insulin therapy did not suppress autoimmune reactions towards the beta cells.

Effect of Photopheresis on Lymphocyte Population in Children with Newly Diagnosed Type 1 Diabetes

“…Several studies have reported that physical, psychological, or chemical stress can produce imbalances in the proportions of T-cell subsets, immunoglobulin levels, and lymphocyte reactivity (6,25,32). Since it became evident that type 1 diabetes may be caused by an autoimmune process, several types of immune interventions have been tried, mostly with minor or transient effects (4,15,19,22,27,33). Photopheresis has been claimed to be an effective form of immunomodulation (37), and it has been used with positive results for the treatment of several immunological diseases, such as rheumatoid arthritis (29), systemic lupus erythematosus (21), psoriatic arthritis (34), and cutaneous T-cell lymphoma (7).…”